TITLE:
Phosphorylation on TRPV4 Serine Residue 824 Enhances Its Association with PGM1
AUTHORS:
Sung Hwa Shin, Eun Jeoung Lee, Sunghee Hyun, Sang Sun Kang
KEYWORDS:
Membrane Localization, Phosphoglucomutase1, Phosphorylation, Protein-Protein Interaction, TRPV4
JOURNAL NAME:
American Journal of Molecular Biology,
Vol.6 No.1,
January
7,
2016
ABSTRACT: The TRPV4 cation channel is expressed in a broad range of tissues and participates in the generation
of a Ca2+ signal and/or depolarization of membrane potential. Here, human phosphoglucomutase-
1 (PGM1), an enzyme that converts glucose-6 phosphate to glucose-1 phosphate in the glycolysis
pathway, as the first auxiliary protein of TRPV4 Ca2+ channels, is identified with yeast two
hybrid system, coimmunoprecipitation, confocal microscopy, and GST pull-down assays. TRPV4
forms a complex with PGM1 through its C-terminal cytoplasmic domain. Because it is demonstrated
that TRPV4 serine residue 824 (S824) is phosphorylated by serum/glucocorticoid regulated
kinase 1, we elucidate the effect of TRPV4 S824 phosphorylation on TRPV association with
PGM1. Even an inactivated mutant version of TRPV4, S824A, exhibited a decreased ability to bind
PGM1, an activated phosphomimetic mutant version of TRPV4, S824D, exhibited enhanced binding
to PGM1. Thus, formation of the TRPV4/PGM1 complex and localization of this complex to the
plasma membrane appear to be regulated by the phosphorylation status of residue S824 in TRPV4.
The newly identified interactor of TRPV4 may help the molecular pathways modulating transport
activity or glucose metabolism, respectively.